Hamilton J D, O'Flaherty E J
Toxicology Department, Rohm and Haas Company, Spring House, Pennsylvania 19477, USA.
Fundam Appl Toxicol. 1995 Jul;26(2):265-71. doi: 10.1006/faat.1995.1097.
Lead will inhibit skeletal development and localize in areas of bone formation and resorption, but the mechanisms of lead toxicity in bone are largely unknown. This study used an ectopic bone (plaque) induction method to investigate the effect of lead on mineralization of cartilage in growing bone. Demineralized bone matrix was subcutaneously implanted in male Long-Evans rats to induce plaque formation. Of 64 rats which were provided deionized water, 32 were implanted with control matrix (control group). The remaining 32 rats were implanted with matrix containing a target concentration of 200 micrograms lead/g of plaque tissue as ectopic bone (lead-added group). Another group of 32 rats was continuously exposed to 1000 ppm lead in drinking water and subcutaneously implanted with control matrix (drinking water-lead group). Plaques were taken for analysis on Days 8 and 12 postimplantation. Alkaline phosphatase activity and cartilage mineralization were obliterated in lead-added plaques. However, calcium deposition was markedly enhanced in the lead-added plaques. Decreased alkaline phosphatase in Day 8 drinking water-lead plaques followed increased Day 12 drinking water lead plaque calcification. Enhanced cartilage calcification and reduced alkaline phosphatase activity in the drinking water-lead plaques was consistent with effects observed in the metaphyseal regions of bone in lead-exposed rats and pigs. The results of this study suggest that lead adversely influences bone development through disruption of mineralization during growth.
铅会抑制骨骼发育，并在骨形成和吸收区域蓄积，但铅在骨骼中产生毒性的机制在很大程度上尚不清楚。本研究采用异位骨（骨斑）诱导方法来研究铅对生长中骨骼软骨矿化的影响。将脱矿骨基质皮下植入雄性Long-Evans大鼠体内以诱导骨斑形成。在64只饮用去离子水的大鼠中，32只植入对照基质（对照组）。其余32只大鼠植入含目标浓度为200微克铅/克骨斑组织的基质作为异位骨（加铅组）。另一组32只大鼠持续饮用含1000 ppm铅的水，并皮下植入对照基质（饮水加铅组）。在植入后第8天和第12天取出骨斑进行分析。加铅骨斑中的碱性磷酸酶活性和软骨矿化受到抑制。然而，加铅骨斑中的钙沉积明显增强。饮水加铅组第8天骨斑中的碱性磷酸酶降低，随后第12天饮水加铅组骨斑钙化增加。饮水加铅组中软骨钙化增强和碱性磷酸酶活性降低与铅暴露大鼠和猪骨骼干骺端区域观察到的效应一致。本研究结果表明，铅通过干扰生长过程中的矿化对骨骼发育产生不利影响。
